Biocryst expands HAE treatment portfolio with Astria acquisition
Phase 3 navenibart trial is recruiting patients at several locations
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Biocryst Pharmaceuticals has acquired Astria Therapeutics, and with it navenibart, an investigational treatment to prevent swelling attacks in people with hereditary angioedema (HAE).
Navenibart is being tested in the Phase 3 ALPHA-ORBIT trial (NCT06842823), which is recruiting patients, ages 12 and older with HAE type 1 or 2, at several locations worldwide. Top-line results are expected in 2027 and may set the basis for navenibart’s approval.
Navenibart adds to Byocryst’s HAE portfolio, which includes Orladeyo (berotralstat), an oral treatment approved to prevent swelling attacks in children and adults with HAE. According to the company, this offers physicians and patients the opportunity to choose the best options for individualized care.
HAE is caused by genetic mutations that usually impair the production or function of the C1-inhibitor (C1-INH) protein. Without C1-INH, an enzyme called kallikrein becomes overactive, triggering the release of bradykinin. High bradykinin levels result in more permeable blood vessels, allowing fluid to leak into tissues and causing swelling.
Navenibart is an antibody-based therapy designed to block kallikrein, reducing bradykinin levels and preventing HAE swelling attacks. It is a long-acting treatment that may be administered every three to six months by subcutaneous (under-the-skin) injection. This is a less frequent dosing than most other injectable treatments, which can ease treatment burden for people with HAE.
Dosing schedule aims to improve patient experience
In the Phase 2 ALPHA-STAR trial (NCT05695248), navenibart was well tolerated and reduced the rate of monthly swelling attacks by 90% to 95% in people with HAE. In the ALPHA-SOLAR Phase 2 (NCT06007677) trial, an open-label extension study, navenibart reduced swelling attacks by a mean of 92% over 10 months of follow-up, demonstrating a sustained benefit.
The ALPHA-ORBIT trial expects to enroll 145 patients, who will be randomly assigned to receive navenibart or a placebo by subcutaneous injection, using one of three dosing schedules: 600 mg every three months, 600 mg every six months, or 600 mg initially followed by 300 mg every three months. Adolescents will all receive navenibart, starting with 600 mg, then 300 mg every three months.
The trial’s main goal is to assess the number of swelling attacks during the six-month treatment period. Secondary measures include assessing the number of moderate to severe attacks, time to first attack, and the proportion of patients who respond to the treatment. After completing the trial, patients may continue the treatment in ORBIT-EXPANSE, where they will receive the therapy at a fixed dose every three to six months.
Navenibart has the potential to become the first HAE therapy to effectively prevent swelling attacks with three- and six-month dosing, which may significantly improve the treatment experience for HAE patients, according to a Biocryst press release.
Biocryst acquired Astria for about $700 million, paid in cash and shares. As part of the acquisition agreement, Jill C. Milne, PhD, co-founder and CEO of Astria, has joined the Biocryst board.
John Ruesch, senior vice president of pharmaceutical sciences and technical operations at Astria, has also joined Biocryst as chief technical operations officer to support the advancement and commercialization of navenibart.
